PK, Dose Proportionality, Food Effect And Repeat Dose Study Of Rosiglitazone XR In Healthy Volunteers
Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Alzheimer's Disease
Intervention: Rosiglitazone XR (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: GlaxoSmithKline Official(s) and/or principal investigator(s): GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline
Summary
The present pharmacokinetic study is designed to further characterise the pharmacokinetics
of the RSG XR formulation and aims to assess dose proportionality, strength equivalence, the
food effect and the pharmacokinetics after repeat dosing.
Clinical Details
Official title: A Two Cohort Study in Healthy Volunteers to Characterise the Pharmacokinetic Properties of the Rosiglitazone XR Formulation Manufactured at the GlaxoSmithKline Crawley Facility.
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: •For the single dose period: AUC(0-inf) and Cmax of RSG XR.•For repeat dose period on Day 1 and 6:, AUC(0-24) and Cmax of RSG XR.
Secondary outcome: For single dose period: AUC(0-t), Tmax, lz, and t1/2 of RSG XR as data permitFor repeat dose period: Tmax, concentration at the end of the dosing interval (Ct), minimum observed concentration (Cmin), Average concentration during a dosing interval (Cav), t1/2, , accumulation ratio(Rs) Rs= (AUC(0-t) last day)/(AUC(0-t) first day) and degree of fluctuation DF= (Cmax-Cmin)/Cave. • Safety reporting (adverse events, laboratory testing, ECG, vital signs)
Detailed description:
The present pharmacokinetic study is designed to further characterise the pharmacokinetics
of the RSG XR formulation manufactured in Crawley and aims to assess dose proportionality,
strength equivalence, the food effect and the pharmacokinetics after repeat dosing. The
study aims to enroll sufficient number of subjects to ensure 48 subjects complete Study Part
1 (6 period crossover design) and a further 12 subjects complete Study Part 2 (repeat
dosing).
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
A subject will be eligible for inclusion in this study only if all of the following
criteria apply:
Healthy male and female (not gender stratified) subjects aged 18-55 years inclusive -
healthy subjects are defined as individuals who are free from clinically significant
illness or disease as determined by their medical history, physical examination,
laboratory studies, ECGs, and other tests. A subject with clinical abnormality or
laboratory parameters outside the reference range for this age group may be included only
if the Investigator and the GSK Medical Monitor considers that the findings will not
introduce additional risk factors and will not interfere with the study procedures.
Body weight greater than 50 kg (110lbs and Body mass index (BMI) between 19 and 30 kg/m2
Willing and able to give written informed consent, willing to participate for the full
duration of the study, and able to understand and follow instructions related to study
procedures.
Female subjects able to bear children must agree to use an adequate method of
contraception for the duration of the study and for 14 days after last dose (see for
details of highly effective methods to avoid pregnancy). Female subjects who are
pre-menopausal or who have been post-menopausal for less than 2 years must undertake
pregnancy testing (serum test) less than or equal to 7 days before Visit 1, which must be
negative
Females, who are on hormone replacement therapy (HRT), and whose menopausal status is in
doubt, will be required to use a highly effective method to avoid pregnancy, as outlined
in the protocol, if they wish to continue their HRT during the study. Otherwise, they must
discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and
the blood draw; this interval depends on the type and dosage of HRT. Following
confirmation of their post-menopausal status, they can resume use of HRT during the study
without use of a highly effective method to avoid pregnancy.
Exclusion Criteria:
A subject will not be eligible for inclusion in this study if any of the following
criteria apply:
Any clinically relevant abnormality identified on the screening history and physical or
laboratory examination or any other medical condition or circumstance making the volunteer
unsuitable for participation in the study. Specific examples include, coronary artery
disease, myocardial infarction, congestive heart failure, type 2 diabetes, renal disease
and hypertension. If there is doubt on the appropriateness of a subject, that subject's
eligibility for the study must be reviewed with the medical monitor prior to enrolment.
History of surgical procedures that might affect the absorption of rosiglitazone (e. g.,
partial/total gastrectomy, cholecystectomy) or any hepatic or biliary abnormalities such
as Gilbert's syndrome.
History of regular alcohol consumption exceeding 7 drinks/week for females or 14
drinks/week for men (1 drink = 150mls of wine or 360mls of beer or 45mls of hard liquor)
within 6 months of screening.
Subject smoking more than 10 cigarettes per day. Positive urine drug screen (UDS)
including alcohol at screening or check-in visits.
Positive hepatitis B virus, hepatitis C virus or HIV test at screening. Positive serum
beta-human chorionic gonadotropin test (females). Women who are pregnant, lactating, or
planning to become pregnant. Male subjects who are not willing to abstain from or use a
condom during sexual intercourse with pregnant or lactating females. Male subjects not
willing to use a condom, plus another form of contraception (e. g., spermicide, IUD, birth
control pills taken by female partner, diaphragm with spermicide) if engaging in sexual
intercourse with a female who could become pregnant. Male subjects not willing to adhere
to these contraceptive criteria from administration of study medication until completion
of follow-up procedures.
Female subjects not willing to use proposed contraceptive methods. Use of prescription or
non-prescription drugs [in particular known inhibitors of cytochrome 2C8 (Gemfibrozil,
trimethoprim, glitazone, monteleucast, quercetin) or inducer (rifampin)], vitamins, herbal
and dietary supplements (including St. John's Wort) within 14 days or 5 half-lives
(whichever is longer) prior to the first dose of study medication. Excluded from this
list are acetaminophen and paracetamol at doses of less than or equal to 2 grams/day,
thyroid replacement therapy, and hormonal methods of contraception (including oral
contraceptives, injectable progesterone, progestin subdermal implants and
progesterone-releasing IUDs, but NOT postcoital contraceptive methods) and hormone
replacement therapy which will be permitted throughout the study.
Donation of blood in excess of 500 mL within 56 days prior to first dose of study
medication.
History of sensitivity to heparin, heparin-induced thrombocytopenia or sensitivity to any
of the study medications or components thereof.
History of hypersensitivity to rosiglitazone, or any of the excipients in the
formulations.
Systolic BP greater than 140 mm Hg and/or Diastolic BP greater than 90 mm Hg at screening
or check-in.
QTc (machine read) greater than 450 ms on the screening ECG. History of glucose
intolerance (serum glucose greater than 110 mg/dl or 6. 1 mmol/L after 8 hours fasting)
Subjects have had treatment with a new molecular entity (investigational drug) or any
other trial during the previous 30 days or five half-lives, whichever is longer. (the
washout is from last dose of study medication in the previous study until the first dose
of study medication).
Current evidence of drug abuse or history of drug abuse within one year of allocation
Inability to understand the protocol requirements, instructions and study-related
restrictions, the nature, scope, and possible consequences of the study Unlikely to comply
with the protocol requirements, instructions and study-related restrictions; e. g.,
uncooperative attitude, inability to return for follow-up visits, and improbability of
completing the study Subject is the investigator or any sub-investigator, research
assistant, pharmacist, study coordinator, other staff or relative thereof directly
involved in the conduct of the study.
Vulnerable subjects (e. g. persons kept in detention).
Locations and Contacts
GSK Investigational Site, Berlin 14050, Germany
Additional Information
Starting date: August 2008
Last updated: May 31, 2012
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